Conifers Phytochemicals: Comparison
Please note this is a comparison between Version 2 by Conner Chen and Version 1 by Natália Cruz-Martins.

The phytochemical constituents present in conifer extracts are nontoxic at therapeutic levels, with polyphenolic compounds having significant biological activities. Stilbenes, terpenes, alkaloids, lignins and flavanoids, such as quercetin, rutin, resveratrol, and the compounds PYC and enzogenol, are the phytochemical components of conifer extracts reported to have sedative, antidiabetic, anticancer and anesthetic effects. In addition, phytochemicals present in conifer extracts assist in the regulation of glucose and lipid metabolism, insulin secretion, stimulating β cells, the NF-kB signaling pathway, the inhibition of gluconeogenic enzymes, ROS protective action as well as targeting and modulating cytokines which affect neuron cells and reduce oxidative stress.

  • conifers
  • phytoconstituent
  • biological effects
  • phytomedicine
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References

  1. Mustafa, G.; Arif, R.; Atta, A.; Sharif, S.; Jamil, A. Bioactive Compounds from Medicinal Plants and Their Importance in Drug Discovery in Pakistan. Matrix Sci. Pharma 2017, 1, 17–26.
  2. Abdel-Razek, A.S.; El-Naggar, M.E.; Allam, A.; Morsy, O.M.; Othman, S.I. Microbial natural products in drug discovery. Processes 2020, 8, 470.
  3. Yuan, H.; Ma, Q.; Ye, L.; Piao, G. The traditional medicine and modern medicine from natural products. Molecules 2016, 21, 559.
  4. Nisar, B.; Sultan, A.; Rubab, S.L. Comparison of Medicinally Important Natural Products versus Synthetic Drugs-A Short Commentary. Nat. Prod. Chem. Res. 2018, 06, 308.
  5. Newman, D.J.; Cragg, G.M.; Snader, K.M. Natural products as sources of new drugs over the period 1981–2002. J. Nat. Prod. 2003, 66, 1022–1037.
  6. Galm, U.; Shen, B. Natural Product Drug Discovery: The Times Have Never Been Better. Chem. Biol. 2007, 14, 1098–1104.
  7. Akaberi, M.; Boghrati, Z.; Amiri, M.S.; Khayyat, M.H.; Emami, S.A. A Review of Conifers in Iran: Chemistry, Biology and their Importance in Traditional and Modern Medicine. Curr. Pharm. Des. 2020, 26, 1584–1613.
  8. Bhardwaj, K.; Islam, M.T.; Jayasena, V.; Sharma, B.; Sharma, S.; Sharma, P.; Kuča, K.; Bhardwaj, P. Review on essential oils, chemical composition, extraction, and utilization of some conifers in Northwestern Himalayas. Phyther. Res. 2020, 34, 2889–2910.
  9. Bhardwaj, K.; Dhanjal, D.S.; Sharma, A.; Nepovimova, E.; Kalia, A.; Thakur, S.; Bhardwaj, S.; Chopra, C.; Singh, R.; Verma, R.; et al. Conifer-derived metallic nanoparticles: Green synthesis and biological applications. Int. J. Mol. Sci. 2020, 21, 9028.
  10. Conifers. Available online: (accessed on 15 March 2021).
  11. Farjon, A. The Kew Review Conifers of the World. Kew Bull. 2018, 5974, 1–16.
  12. Kopaczyk, J.M.; Warguła, J.; Jelonek, T. The variability of terpenes in conifers under developmental and environmental stimuli. Environ. Exp. Bot. 2020, 180, 104197.
  13. Virjamo, V.; Fyhrquist, P.; Koskinen, A.; Lavola, A.; Nissinen, K.; Julkunen-Tiitto, R. 1,6-Dehydropinidine Is an Abundant Compound in Picea abies (Pinaceae) Sprouts and 1,6-Dehydropinidine Fraction Shows Antibacterial Activity against Streptococcus equi Subsp. equi. Molecules 2020, 25, 4558.
  14. Mill, R.R.; Chase, M.W. A new classification and linear sequence of extant gymnosperms. Phytotaxa 2011, 19, 55–70.
  15. St-Pierre, A.; Blondeau, D.; Bourdeau, N.; Bley, J.; Desgagné-Penix, I. Chemical Composition of Black Spruce (Picea mariana) Bark Extracts and Their Potential as Natural Disinfectant. Ind. Biotechnol. 2019, 15, 219–231.
  16. Tawara, J.N.; Blokhin, A.; Foderaro, T.A.; Stermitz, F.R.; Hope, H. Toxic Piperidine Alkaloids from Pine (Pinus) and Spruce (Picea) Trees. New Structures and a Biosynthetic Hypothesis. J. Org. Chem. 1993, 58, 4813–4818.
  17. Küpeli, E.; Erdemoǧlu, N.; Yeşilada, E.; Şener, B. Anti-inflammatory and antinociceptive activity of taxoids and lignans from the heartwood of Taxus baccata L. J. Ethnopharmacol. 2003, 89, 265–270.
  18. Juyal, D.; Thawani, V.; Thaledi, S.; Joshi, M. Ethnomedical properties of Taxus wallichiana Zucc. (Himalayan yew). J. Tradit. Complement. Med. 2014, 4, 159–161.
  19. Hafezi, K.; Hemmati, A.A.; Abbaszadeh, H.; Valizadeh, A.; Makvandi, M. Anticancer activity and molecular mechanisms of α-conidendrin, a polyphenolic compound present in Taxus yunnanensis, on human breast cancer cell lines. Phyther. Res. 2020, 34, 1397–1408.
  20. Ivanova, D.I.; Tashev, A.N.; Nedialkov, P.T.; Ilieva, Y.E.; Atanassova, T.N.; Olech, M.; Nowak, R.; Angelov, G.; Tsvetanova, F.V.; Iliev, I.A.; et al. Antioxidant and antiproliferative activity of Juniperus L. Species of Bulgarian and foreign origin and their anticancer metabolite identification. Bulg. Chem. Commun. 2018, 50, 144–150.
  21. Kanchan, B.; Prerna, B.; Simran, K. Medicinal value of secondary metabolites of pines grown in Himalayan region of India. Res. J. Biotechnol. 2020, 15, 131–140.
  22. Singh, S.K.; Shanmugavel, M.; Kampasi, H.; Singh, R.; Mondhe, D.M.; Rao, J.M.; Adwankar, M.K.; Saxena, A.K.; Qazi, G.N. Chemically standardized isolates from Cedrus deodara stem wood having anticancer activity. Planta Med. 2007, 73, 519–526.
  23. Jang, Y.P.; Kim, S.R.; Choi, Y.H.; Kim, J.; Kim, S.G.; Markelonis, G.J.; Oh, T.H.; Kim, Y.C. Arctigenin protects cultured cortical neurons from glutamate-induced neurodegeneration by binding to kainate receptor. J. Neurosci. Res. 2002, 68, 233–240.
  24. Asmi, K.S.; Lakshmi, T.; Balusamy, S.R.; Parameswari, R. Therapeutic aspects of taxifolin—An update. J. Adv. Pharm. Educ. Res. 2017, 7, 187–189.
  25. Hammerbacher, A.; Kandasamy, D.; Ullah, C.; Schmidt, A.; Wright, L.P.; Gershenzon, J. Flavanone-3-hydroxylase plays an important role in the biosynthesis of spruce phenolic defenses against bark beetles and their fungal associates. Front. Plant Sci. 2019, 10, 1–15.
  26. Michael, H.N.; Awad, H.M.; El-Sayed, N.H.; Paré, P.W. Chemical and antioxidant investigations: Norfolk pine needles (Araucaria excelsa). Pharm. Biol. 2010, 48, 534–538.
  27. Ferreira-Santos, P.; Genisheva, Z.; Botelho, C.; Santos, J.; Ramos, C.; Teixeira, J.A.; Rocha, C.M.R. Unravelling the biological potential of Pinus pinaster bark extracts. Antioxidants 2020, 9, 334.
  28. Gascón, S.; Jiménez-Moreno, N.; Jiménez, S.; Quero, J.; Rodríguez-Yoldi, M.J.; Ancín-Azpilicueta, C. Nutraceutical composition of three pine bark extracts and their antiproliferative effect on Caco-2 cells. J. Funct. Foods 2018, 48, 420–429.
  29. Dziedzinski, M.; Kobus-Cisowska, J.; Szymanowska, D.; Stuper-Szablewska, K.; Baranowska, M. Identification of polyphenols from coniferous shoots as natural antioxidants and antimicrobial compounds. Molecules 2020, 25, 3527.
  30. Fierascu, I.; Ungureanu, C.; Avramescu, S.M.; Cimpeanu, C.; Georgescu, M.I.; Fierascu, R.C.; Ortan, A.; Sutan, A.N.; Anuta, V.; Zanfirescu, A.; et al. Genoprotective, antioxidant, antifungal and anti-inflammatory evaluation of hydroalcoholic extract of wild-growing Juniperus communis L. (Cupressaceae) native to Romanian southern sub-Carpathian hills. BMC Complement. Altern. Med. 2018, 18, 1–15.
  31. Branco, C.S.; Duong, A.; Machado, A.K.; Wu, A.; Scola, G.; Andreazza, A.C.; Salvador, M. Araucaria angustifolia (Bertol.) Kuntze has neuroprotective action through mitochondrial modulation in dopaminergic SH-SY5Y cells. Mol. Biol. Rep. 2019, 46, 6013–6025.
  32. Nisar, M.; Khan, I.; Ahmad, B.; Ali, I.; Ahmad, W.; Choudhary, M.I. Antifungal and antibacterial activities of Taxus wallichiana Zucc. J. Enzym. Inhib. Med. Chem. 2008, 23, 256–260.
  33. Freitas, A.M.; Almeida, M.T.R.; Andrighetti-Fröhner, C.R.; Cardozo, F.T.G.S.; Barardi, C.R.M.; Farias, M.R.; Simões, C.M.O. Antiviral activity-guided fractionation from Araucaria angustifolia leaves extract. J. Ethnopharmacol. 2009, 126, 512–517.
  34. Al-Sayed, E.; Gad, H.A.; El-Shazly, M.; Abdel-Daim, M.M.; Nasser Singab, A. Anti-inflammatory and analgesic activities of cupressuflavone from Cupressus macrocarpa: Impact on pro-inflammatory mediators. Drug Dev. Res. 2018, 79, 22–28.
  35. Ferrentino, G.; Haman, N.; Morozova, K.; Tonon, G.; Scampicchio, M. Phenolic compounds extracted from spruce (Picea abies) by supercritical carbon dioxide as antimicrobial agents against gram-positive bacteria assessed by isothermal calorimetry. J. Therm. Anal. Calorim. 2020.
  36. Hoon, L.Y.; Choo, C.; Watawana, M.I.; Jayawardena, N.; Waisundara, V.Y. Evaluation of the total antioxidant capacity and antioxidant compounds of different solvent extracts of Chilgoza Pine nuts (Pinus gerardiana). J. Funct. Foods 2015, 18, 1014–1021.
  37. Lee, S.J.; Lee, S.Y.; Hur, S.J.; Bae, Y., II; Jeong, C.H. Neuroprotective and antioxidant effects of Metasequoia glyptostroboides leaf extract. Curr. Top. Nutraceutical Res. 2016, 14, 67–72.
  38. Sahin Yaglioglu, A.; Eser, F. Screening of some Juniperus extracts for the phenolic compounds and their antiproliferative activities. S. Afr. J. Bot. 2017, 113, 29–33.
  39. Osuna-Torres, L.; García-Martí, X.; Ventura-Zapata, E.; López-Upton, J.; Zamilpa-Alvarez, A.; González-Cortazar, M.; Herrera-Ruiz, M.; Tapia-Barrera, N. Taxus globosa Schltdl. (Mexican yew) and Taxus baccata L. (European yew): Intra and interspecies analysis of taxol content and biological activity according to different sources. For. Syst. 2015, 24, 16.
  40. Legault, J.; Girard-Lalancette, K.; Dufour, D.; Pichette, A. Antioxidant potential of bark extracts from boreal forest conifers. Antioxidants 2013, 2, 77–89.
  41. Lantto, T.A.; Colucci, M.; Závadová, V.; Hiltunen, R.; Raasmaja, A. Cytotoxicity of curcumin, resveratrol and plant extracts from basil, juniper, laurel and parsley in SH-SY5Y and CV1-P cells. Food Chem. 2009, 117, 405–411.
  42. Välimaa, A.L.; Raitanen, J.E.; Tienaho, J.; Sarjala, T.; Nakayama, E.; Korpinen, R.; Mäkinen, S.; Eklund, P.; Willför, S.; Jyske, T. Enhancement of Norway spruce bark side-streams: Modification of bioactive and protective properties of stilbenoid-rich extracts by UVA-irradiation. Ind. Crops Prod. 2020, 145, 112150.
  43. Raiber, S.; Schröder, G.; Schröder, J. Molecular and enzymatic characterization of two stilbene synthases from Eastern white pine (Pinus strobus) A single Arg/His difference determines the activity and the pH dependence of the enzymes. FEBS Lett. 1995, 361, 299–302.
  44. Hovelstad, H.; Leirset, I.; Oyaas, K.; Fiksdahl, A. Screening analyses of pinosylvin stilbenes, resin acids and lignans in Norwegian conifers. Molecules 2006, 11, 103–114.
  45. Francezon, N.; Meda, N.S.B.R.; Stevanovic, T. Optimization of bioactive polyphenols extraction from Picea mariana bark. Molecules 2017, 22, 2118.
  46. Latva-Mäenpää, H. Bioactive and Protective Polyphenolics From Roots and Stumps of Conifer Trees (Norway Spruce and Scots Pine); Helsingin Yliopisto: Helsinki, Finland, 2017; ISBN 9789515134653.
  47. Singh, B.; Sharma, R.A. Plant terpenes: Defense responses, phylogenetic analysis, regulation and clinical applications. 3 Biotech 2015, 5, 129–151.
  48. Porres-Martínez, M.; González-Burgos, E.; Carretero, M.E.; Pilar Gómez-Serranillos, M. In vitro neuroprotective potential of the monoterpenes α-pinene and 1,8-cineole against H2O2-induced oxidative stress in PC12 cells. Z. fur Naturforsch. Sect. C J. Biosci. 2016, 71, 191–199.
  49. Da Silveira E Sá, R.D.C.; Andrade, L.N.; De Sousa, D.P. Sesquiterpenes from essential oils and anti-inflammatory activity. Nat. Prod. Commun. 2015, 10, 1767–1774.
  50. Dey, P.; Kundu, A.; Kumar, A.; Gupta, M.; Lee, B.M.; Bhakta, T.; Dash, S.; Kim, H.S. Analysis of Alkaloids (Indole Alkaloids, Isoquinoline Alkaloids, Tropane Alkaloids); Elsevier Inc.: Amsterdam, The Netherlands, 2020; ISBN 9780128164556.
  51. Thawabteh, A.; Juma, S.; Bader, M.; Karaman, D.; Scrano, L.; Bufo, S.A.; Karaman, R. The biological activity of natural alkaloids against herbivores, cancerous cells and pathogens. Toxins 2019, 11, 656.
  52. Ignat, I.; Volf, I.; Popa, V.I. A critical review of methods for characterisation of polyphenolic compounds in fruits and vegetables. Food Chem. 2011, 126, 1821–1835.
  53. Tanase, C.; Boz, I.; Stingu, A.; Volf, I.; Popa, V.I. Physiological and biochemical responses induced by spruce bark aqueous extract and deuterium depleted water with synergistic action in sunflower (Helianthus annuus L.) plants. Ind. Crops Prod. 2014, 60, 160–167.
  54. Tanase, C.; Cosarcă, S.; Muntean, D.L. A critical review of phenolic compounds extracted from the bark of woody vascular plants and their potential biological activity. Molecules 2019, 24, 1182.
  55. El Omari, N.; Ezzahrae Guaouguaou, F.; El Menyiy, N.; Benali, T.; Aanniz, T.; Chamkhi, I.; Balahbib, A.; Taha, D.; Shariati, M.A.; Zengin, G.; et al. Phytochemical and biological activities of Pinus halepensis mill., and their ethnomedicinal use. J. Ethnopharmacol. 2021, 268, 113661.
  56. Metsämuuronen, S.; Sirén, H. Bioactive phenolic compounds, metabolism and properties: A review on valuable chemical compounds in Scots pine and Norway spruce. Phytochem. Rev. 2019, 18, 623–664, ISBN 0123456789.
  57. Rodríguez-García, C.; Sánchez-Quesada, C.; Gaforio, J.J.; Gaforio, J.J. Dietary flavonoids as cancer chemopreventive agents: An updated review of human studies. Antioxidants 2019, 8, 137.
  58. Tsao, R. Chemistry and Biochemistry of Dietary Polyphenols. Nutrients 2010, 2, 1231–1246.
  59. Nanda, S.; Mohanty, J.N.; Mishra, R.; Joshi, R.K. Metabolic Engineering of Phenylpropanoids in Plants. In Transgenesis and Secondary Metabolism; Springer: Berlin/Heidelberg, Germany, 2017; pp. 485–510.
  60. Saleem, M.; Kim, J.; Ali, S.; Sup, Y. An update on bioactive plant lignans. Nat. Prod. Rep. 2005, 22, 696–716.
  61. García-Pérez, M.E.; Royer, M.; Herbette, G.; Desjardins, Y.; Pouliot, R.; Stevanovic, T. Picea mariana bark: A new source of trans-resveratrol and other bioactive polyphenols. Food Chem. 2012, 135, 1173–1182.
  62. Salminen, J.; Karonen, M. Chemical ecology of tannins and other phenolics: We need a change in approach. Br. Ecol. Soc. 2011, 25, 325–338.
  63. Raitanen, J.E.; Järvenpää, E.; Korpinen, R.; Mäkinen, S.; Hellström, J.; Kilpeläinen, P.; Liimatainen, J.; Ora, A.; Tupasela, T.; Jyske, T. Tannins of conifer bark as Nordic piquancy—sustainable preservative and aroma? Molecules 2020, 25, 567.
  64. Koche, D.; Shirsat, R.; Kawale, M. An overview of major classes of phytochemicals: Their type and role in disease prevention. Hislopia J. 2016, 9, 2016.
  65. Prothmann, J.; Sun, M.; Spégel, P.; Sandahl, M.; Turner, C.; Scheuba, J.; Wronski, V.K.; Rollinger, J.M.; Grienke, U.; Santos-Buelga, C.; et al. Relationship between phenolic compounds, anthocyanins content and antioxidant activity in colored barley germplasm. J. Agric. Food Chem. 2017, 53, 1713.
  66. Matthews, S.; Mila, I.; Scalbert, A.; Donnelly, D.M.X. Extractable and non-extractable proanthocyanidins in barks. Phytochemistry 1997, 45, 405–410.
  67. Koleckar, V.; Kubikova, K.; Rehakova, Z.; Kuca, K.; Jun, D.; Jahodar, L.; Opletal, L. Condensed and Hydrolysable Tannins as Antioxidants Influencing the Health. Mini-Rev. Med. Chem. 2008, 8, 436–447.
  68. De Bruyne, T.; Pieters, L.; Deelstra, H.; Vlietinck, A. Condensed vegetable tannins: Biodiversity in structure and biological activities. Biochem. Syst. Ecol. 1999, 27, 445–459.
  69. Scalbert, A. Antimicrobial properties of tannins. Phytochemistry 1991, 30, 3875–3883.
  70. Bhangale, J.O.; Acharya, S.R. Anti-Parkinson Activity of Petroleum Ether Extract of Ficus religiosa (L.) Leaves. Adv. Pharmacol. Sci. 2016, 2016, 9436106.
  71. Brijesh, K.; Ruchi, R.; Sanjita, D.; Saumya, D.; June, A. Phytoconstituents and Therapeutic potential of Thuja occidentalis. Res. J. Pharm. Biol. Chem. Sci. 2012, 3, 354–362.
  72. Shuaib, M.; Ali, M.; Ahamad, J.; Naquvi, K.J.; Ahmad, M.I. Pharmacognosy of Pinus roxburghii: A Review. Phytochemistry 2006, 2, 262–268.
  73. Poudel, R.C.; Gao, L.M.; Möller, M.; Baral, S.R.; Uprety, Y.; Liu, J.; Li, D.Z. Yews (Taxus) along the Hindu Kush-Himalayan region: Exploring the ethnopharmacological relevance among communities of Mongol and Caucasian origins. J ethnopharmacol. 2013, 147, 190–203.
  74. Kunwar, R.M.; Shrestha, K.P.; Bussmann, R.W. Traditional herbal medicine in Far-west Nepal: A pharmacological appraisal. J. Ethnobiol. Ethnomed. 2010, 6, 1–18.
  75. Sharma, H.; Garg, M. A review of traditional use, phytoconstituents and biological activities of Himalayan yew, Taxus wallichiana. J. Integr. Med. 2015, 13, 80–90.
  76. Di Meo, S.; Reed, T.T.; Venditti, P.; Victor, V.M. Role of ROS and RNS Sources in Physiological and Pathological Conditions. Oxid. Med. Cell. Longev. 2016, 2016, 1245049.
  77. Phaniendra, A.; Jestadi, D.B.; Periyasamy, L. Free Radicals: Properties, Sources, Targets, and Their Implication in Various Diseases. Indian J. Clin. Biochem. 2015, 30, 11–26.
  78. Kumar, H.; Bhardwaj, K.; Nepovimova, E.; Kuča, K.; Dhanjal, D.S.; Bhardwaj, S.; Bhatia, S.K.; Verma, R.; Kumar, D. Antioxidant functionalized nanoparticles: A combat against oxidative stress. Nanomaterials 2020, 10, 1334.
  79. Collin, F. Chemical basis of reactive oxygen species reactivity and involvement in neurodegenerative diseases. Int. J. Mol. Sci. 2019, 20, 2407.
  80. Genestra, M. Oxyl radicals, redox-sensitive signalling cascades and antioxidants. Cell. Signal. 2007, 19, 1807–1819.
  81. Ricordi, C.; Garcia-Contreras, M.; Farnetti, S. Diet and Inflammation: Possible Effects on Immunity, Chronic Diseases, and Life Span. J. Am. Coll. Nutr. 2015, 34, 10–13.
  82. Boukhenouna, S.; Wilson, M.A.; Bahmed, K.; Kosmider, B. Reactive oxygen species in chronic obstructive pulmonary disease. Oxid. Med. Cell. Longev. 2018, 2018, 5730395.
  83. Packer, L.; Rimbach, G.; Virgili, F. Antioxidant activity and biologic properties of a procyanidin-rich extract from pine (Pinus maritima) bark, pycnogenol. Free Radic. Biol. Med. 1999, 27, 704–724.
  84. Lobo, V.; Patil, A.; Phatak, A.; Chandra, N. Free radicals, antioxidants and functional foods: Impact on human health. Pharmacogn. Rev. 2010, 4, 118–126.
  85. Iravani, S.; Zolfaghari, B. Pharmaceutical and nutraceutical effects of Pinus pinaster bark extract. Res. Pharm. Sci. 2011, 6, 1–11.
  86. Senthilmohan, S.T.; Zhang, J.; Stanley, R.A. Effects of flavonoid extract Enzogenol with vitamin C on protein oxidation and DNA damage in older human subjects. Nutr. Res. 2003, 23, 1199–1210.
  87. Azqueta, A.; Collins, A. Polyphenols and DNA damage: A mixed blessing. Nutrients 2016, 8, 785.
  88. Kukreja, A.; Wadhwa, N. Therapeutic Role of Resveratrol and Piceatannol in Disease Prevention. J. Blood Disord. Transfus. 2014, 5, 9.
  89. Sharma, A.; Goyal, R.; Sharma, L. Potential biological efficacy of Pinus plant species against oxidative, inflammatory and microbial disorders. BMC Complement. Altern. Med. 2016, 16, 1–11.
  90. Azab, A.; Nassar, A.; Azab, A.N. Anti-inflammatory activity of natural products. Molecules 2016, 21, 1321.
  91. Artis, D.; Spits, H. The biology of innate lymphoid cells. Nature 2015, 517, 293–301.
  92. Fernandes, J.V.; Cobucci, R.N.O.; Jatobá, C.A.N.; de Medeiros Fernandes, T.A.A.; de Azevedo, J.W.V.; de Araújo, J.M.G. The Role of the Mediators of Inflammation in Cancer Development. Pathol. Oncol. Res. 2015, 21, 527–534.
  93. Heppner, F.L.; Ransohoff, R.M.; Becher, B. Immune attack: The role of inflammation in Alzheimer disease. Nat. Rev. Neurosci. 2015, 16, 358–372.
  94. Rock, K.L.; Rock, K.L. Innate and adaptive immune responses to cell death. Immunol. Rev. 2011, 243, 191–205.
  95. Waisman, A.; Liblau, R.S.; Becher, B. Innate and adaptive immune responses in the CNS. Lancet Neurol. 2015, 14, 945–955.
  96. Vignali, D.A.A.; Kuchroo, V.K. Review IL-12 family cytokines: Immunological playmakers. Nat. Immunol. 2012, 13, 722–728.
  97. Montgomery, S.L.; Bowers, W.J. Tumor Necrosis Factor-alpha and the Roles it Plays in Homeostatic and Degenerative Processes Within the Central Nervous System. J. Neuroimmune Pharmacol. 2012, 7, 42–59.
  98. Fenton, M.J. Review: Transcriptional and post-transcriptional regulation of interleukin 1 gene expression. Int. J. Immunopharm. 1992, 14, 401–411.
  99. Rider, P.; Carmi, Y.; Voronov, E.; Apte, R.N. Interleukin-1α. Semin. Immunol. 2013, 25, 430–438.
  100. Cha, K.-J. The Anti-Inflammatory Effects of Picea wilsonii Mast on HaCaT Cells. Korean J. Clin. Lab. Sci. 2016, 48, 365–370.
  101. Langrish, C.L.; Mckenzie, B.S.; Wilson, N.J.; Kastelein, R.A.; Cua, D.J. IL-12 and IL-23: Master regulators of innate and adaptive immunity. Immunol. Rev. 2004, 202, 96–105.
  102. Duvallet, E.; Semerano, L.; Assier, E.; Falgarone, G.; Duvallet, E.; Semerano, L.; Assier, E.; Falgarone, G.; Duvallet, E.; Semerano, L.; et al. Interleukin-23: A key cytokine in inflammatory diseases. Ann. Med. 2011, 3890, 503–511.
  103. Sabat, R. Cytokine & Growth Factor Reviews IL-10 family of cytokines. Cytokine Growth Factor Rev. 2010, 21, 315–324.
  104. Ng, T.H.S.; Britton, G.J.; Hill, E.V.; Verhagen, J.; Burton, B.R.; Wraith, D.C. Regulation of adaptive immunity; the role of interleukin-10. Front. Immunol. 2013, 4, 1–14.
  105. Kwilasz, A.J.; Grace, P.M.; Serbedzija, P.; Maier, S.F.; Watkins, L.R. Neuropharmacology The therapeutic potential of interleukin-10 in neuroimmune diseases. Neuropharmacology 2014, 2, 55–69.
  106. Atanasov, A.G.; Waltenberger, B.; Pferschy-Wenzig, E.M.; Linder, T.; Wawrosch, C.; Uhrin, P.; Temml, V.; Wang, L.; Schwaiger, S.; Heiss, E.H.; et al. Discovery and resupply of pharmacologically active plant-derived natural products: A review. Biotechnol. Adv. 2015, 33, 1582–1614.
  107. Zhang, Q.W.; Lin, L.G.; Ye, W.C. Techniques for extraction and isolation of natural products: A comprehensive review. Chin. Med. 2018, 13, 1–26.
  108. Bucar, F.; Wube, A.; Schmid, M. Natural product isolation-how to get from biological material to pure compounds. Nat. Prod. Rep. 2013, 30, 525–545.
  109. Gopalasatheeskumar, K. Significant Role of Soxhlet Extraction Process in Phytochemical. Mintage J. Pharm. Med. Sci. 2018, 7, 43–47.
  110. Zhao, Q.Q.; Wang, S.F.; Li, Y.; Song, Q.Y.; Gao, K. Terpenoids with anti-inflammatory activity from Abies chensiensis. Fitoterapia 2016, 111, 87–94.
  111. Qayum, M.; Nisar, M.; Shah, M.R.; Adhikari, A.; Kaleem, W.A.; Khan, I.; Khan, N.; Gul, F.; Khan, I.A.; Zia-Ul-Haq, M.; et al. Analgesic and antiinflammatory activities of taxoids from Taxus wallichiana Zucc. Phyther. Res. 2012, 26, 552–556.
  112. Stan, M.S.; Voicu, S.N.; Caruntu, S.; Nica, I.C.; Olah, N.K.; Burtescu, R.; Balta, C.; Rosu, M.; Herman, H.; Hermenean, A.; et al. Antioxidant and anti-inflammatory properties of a Thuja occidentalis mother tincture for the treatment of ulcerative colitis. Antioxidants 2019, 8, 416.
  113. Kim, D.S.; Kim, M.S.; Kang, S.W.; Sung, H.Y.; Kang, Y.H. Pine bark extract enzogenol attenuated tumor necrosis factor-α- induced endothelial cell adhesion and monocyte transmigration. J. Agric. Food Chem. 2010, 58, 7088–7095.
  114. Schäfer, A.; Chovanová, Z.; Muchová, J.; Sumegová, K.; Liptáková, A.; Högger, P. Inhibition of COX-1 and COX-2 activity by plasma of human volunteers after ingestion of French maritime pine bark extract (Pycnogenol). Biomed. Pharmacother. 2005, 60, 5–9.
  115. Latest Global Cancer Data_ Cancer Burden Rises to 18 2018. WHO. Available online: (accessed on 15 February 2021).
  116. Yan, S.H. An early history of human breast cancer: West meets East. Chin. J. Cancer 2013, 32, 475–477.
  117. Sudhakar, A. History of Cancer, Ancient and Modern Treatment Methods. J. Cancer Sci. Ther. 2009, 01, i–iv.
  118. Ghosh, S.K. Giovanni Battista Morgagni (1682–1771): Father of pathologic anatomy and pioneer of modern medicine. Anat. Sci. Int. 2017, 92, 305–312.
  119. Cancer. Available online: (accessed on 20 February 2021).
  120. Ma, X.; Wang, Z. Anticancer drug discovery in the future: An evolutionary perspective. Drug Discov. Today 2009, 14, 1136–1142.
  121. Widmer, N.; Bardin, C.; Chatelut, E.; Paci, A.; Beijnen, J.; Levêque, D.; Veal, G.; Astier, A. Review of therapeutic drug monitoring of anticancer drugs part two—Targeted therapies. Eur. J. Cancer 2014, 50, 2020–2036.
  122. Kuczynski, E.A.; Sargent, D.J.; Grothey, A.; Kerbel, R.S. Drug rechallenge and treatment beyond progression-implications for drug resistance. Nat. Rev. Clin. Oncol. 2013, 10, 571–587.
  123. Lichota, A.; Gwozdzinski, K. Anticancer activity of natural compounds from plant and marine environment. Int. J. Mol. Sci. 2018, 19, 3533.
  124. Kim, J.A.H.; Kim, D.H.; Hossain, M.A.; Kim, M.Y.; Sung, B.; Yoon, J.H.; Suh, H.; Jeong, T.C.; Chung, H.Y.; Kim, N.D. HS-1793, a resveratrol analogue, induces cell cycle arrest and apoptotic cell death in human breast cancer cells. Int. J. Oncol. 2014, 44, 473–480.
  125. Sharifi-Rad, J.; Ozleyen, A.; Tumer, T.B.; Adetunji, C.O.; El Omari, N.; Balahbib, A.; Taheri, Y.; Bouyahya, A.; Martorell, M.; Martins, N.; et al. Natural products and synthetic analogs as a source of antitumor drugs. Biomolecules 2019, 9, 679.
  126. Tafrihi, M.; Imran, M.; Tufail, T.; Gondal, T.A.; Caruso, G.; Sharma, S.; Sharma, R.; Atanassova, M.; Atanassov, L.; Valere, P.; et al. The Wonderful Activities of the Genus Mentha: Not Only Antioxidant Properties. Molecules 2021, 26, 1118.
  127. Birinci, H.; Şen, B.; Sayğılı, S.; Ölmez, E.; Uluer, E.T.; Özbilgin, K. The Effect of Pycnogenol and Paclitaxel on DNA Damage in Human Breast Cancer Cell Line. Proceedings 2017, 1, 1023.
  128. Dinić, J.; Ríos-Luci, C.; Karpaviciene, I.; Cikotiene, I.; Fernandes, M.X.; Pešić, M.; Padrón, J.M. CKT0353, a novel microtubule targeting agent, overcomes paclitaxel induced resistance in cancer cells. Investig. New Drugs 2020, 38, 584–598.
  129. Binarová, P.; Tuszynski, J. Tubulin: Structure, Functions and Roles in Disease. Cells 2019, 8, 1294.
  130. Zhang, D.; Kanakkanthara, A. Beyond the paclitaxel and vinca alkaloids: Next generation of plant-derived microtubule-targeting agents with potential anticancer activity. Cancers 2020, 12, 1721.
  131. Harshita; Barkat, M.A.; Beg, S.; Pottoo, F.H.; Ahmad, F.J. Nanopaclitaxel therapy: An evidence based review on the battle for next-generation formulation challenges. Nanomedicine 2019, 14, 1323–1341.
  132. Ganguly, A.; Yang, H.; Cabral, F. Paclitaxel-dependent cell lines reveal a novel drug activity. Mol. Cancer Ther. 2010, 9, 2914–2923.
  133. Banerjee, S.; Das, A.; Chakraborty, P.; Suthindhiran, K.; Jayasri, M.A. Antioxidant and antimicrobial activity of Araucaria cookii and Brassaia actinophyla. Pak. J. Biol. Sci. 2014, 17, 715–719.
  134. Jain, S.; Kumar, D.; Malviya, N.; Jain, A.; Jain, S.; Jain, V. Estimation of total phenolic, tannins, and flavonoid contents and antioxidant activity of Cedrus deodara heart wood extracts. Egypt. Pharm. J. 2015, 14, 10.
  135. Horiba, H.; Nakagawa, T.; Zhu, Q.; Ashour, A.; Watanabe, A.; Shimizu, K. Biological activities of extracts from different parts of cryptomeria japonica. Nat. Prod. Commun. 2016, 11, 1337–1342.
  136. Bajpai, V.K.; Sharma, A.; Kang, S.C.; Baek, K.H. Antioxidant, lipid peroxidation inhibition and free radical scavenging efficacy of a diterpenoid compound sugiol isolated from Metasequoia glyptostroboides. Asian Pac. J. Trop. Med. 2014, 7, 9–15.
  137. Bhagat, M.; Gupta, S.; Sudan, R. In vitro Evaluation of Antioxidant Activity of Picea smithiana Growing in Bhaderwah Region of Jammu and Kashmir. Cell. Life Sci. J. 2017, 2.
  138. Salhi, N.; Bouyahya, A.; El Guourrami, O.; El Jemli, M.; Bourais, I.; Zellou, A.; Cherrah, Y.; El Abbes Faouzi, M. Investigation of in vitro and in vivo antioxidant and antidiabetic activities of Pinus halepensis extracts. J. Herbmed Pharmacol. 2021, 10, 123–131.
  139. Tekaday, D.; Antony, B.; Jain, S. Antimicrobial, antioxidant and phytochemical investigation of Thuja occidentalis (Arbor vitae) leave extract. GSC Biol. Pharm. Sci. 2020, 12, 108–116.
  140. Milutinović, M.G.; Stanković, M.S.; Cvetković, D.M.; Topuzović, M.D.; Mihailović, V.B.; Marković, S.D. Antioxidant and anticancer properties of leaves and seed cones from European yew (Taxus baccata L.). Arch. Biol. Sci. 2015, 67, 525–534.
  141. Bhat, M.A.; Ganie, S.A.; Dar, K.B.; Ali, R.; Hamid, R. In Vitro antioxidant potential and hepatoprotective activity of Taxus Wallichiana. Asian J. Pharm. Clin. Res. 2018, 11, 237–243.
  142. Subba, B. Analysis of Phytochemical Constituents and Biological Activity of Taxus Wallichiana Zucc. Dolakha District of Nepal. Int. J. Appl. Sci. Biotechnol. 2018, 6, 110–114.
  143. Yang, X.-W.; Zeng, H.-W.; Liu, X.-H.; Li, S.-M.; Xu, W.; Shen, Y.-H.; Zhang, C.; Zhang, W.-D. Anti-inflammatory and anti-tumour effects of Abies georgei extracts. J. Pharm. Pharmacol. 2008, 60, 937–941.
  144. Nayak, S.S.; Ghosh, A.K.; Debnath, B.; Vishnoi, S.P.; Jha, T. Synergistic effect of methanol extract of Abies webbiana leaves on sleeping time induced by standard sedatives in mice and anti-inflammatory activity of extracts in rats. J. Ethnopharmacol. 2004, 93, 397–402.
  145. Bisht, B.; Nainwal, P.; Saini, P. Evaluation of in vitro anti-inflammatory activity of Agathis robusta. J. Pharma. Res. 2012, 2, 1304–1306.
  146. Journal, A.I. An Indian Journal Note. Anal. Chem. 2007, 6, 4–8.
  147. Orhan, N.; Akkol, E.; Ergun, F. Evaluation of antiinflammatory and antinociceptive effects of some juniperus species growing in Turkey. Turk. J. Biol. 2012, 36, 719–726.
  148. Science, A. Assessment of Anti-Inflammatory Activity of Taxus baccata Linn. Bark Extract Satyajit Dutta * G. Mariappan ** Dipankar Sarkar ** Piyali Sarkar ** Table 1: Effect of Taxus baccata (L) bark extracts on Carrageenan-induced paw edema method in rats. Anc. Sci. Life 2010, 29, 19–21.
  149. Branco, C.D.S.; De Lima, É.D.; Rodrigues, T.S.; Scheffel, T.B.; Scola, G.; Laurino, C.C.F.C.; Moura, S.; Salvador, M. Mitochondria and redox homoeostasis as chemotherapeutic targets of Araucaria angustifolia (Bert.) O. Kuntze in human larynx HEp-2 cancer cells. Chem. Biol. Interact. 2015, 231, 108–118.
  150. Shashi, B.; Jaswant, S.; Madhusudana, R.J.; Kumar, S.A.; Nabi, Q.G. A novel lignan composition from Cedrus deodara induces apoptosis and early nitric oxide generation in human leukemia Molt-4 and HL-60 cells. Nitric Oxide Biol. Chem. 2006, 14, 72–88.
  151. Shi, X.; Liu, D.; Zhang, J.; Hu, P.; Shen, W.; Fan, B.; Ma, Q.; Wang, X. Extraction and purification of total flavonoids from pine needles of Cedrus deodara contribute to anti-tumor in vitro. BMC Complement. Altern. Med. 2016, 16, 1–9.
  152. Basu, L.R.; De, A.; Sarkar, P.; Karak, P.; Dastidar, S.G. Possibilities of developing novel potent antitumor agents from the leaves of Cryptomaria japonica. Int. J. Phytomed. 2016, 8, 404–410.
  153. Fernandez, A.; Cock, I.E. The therapeutic properties of juniperus communis L.: Antioxidant capacity, bacterial growth inhibition, anticancer activity and toxicity. Pharmacogn. J. 2016, 8, 273–280.
  154. Muto, N.; Tomokuni, T.; Haramoto, M.; Tatemoto, H.; Nakanishi, T.; Inatomi, Y.; Murata, H.; Inada, A. Isolation of apoptosis- and differentiation-inducing substances toward human promyelocytic leukemia HL-60 cells from leaves of Juniperus taxifolia. Biosci. Biotechnol. Biochem. 2008, 72, 477–484.
  155. Barnawi, I.O.; Nasr, F.A.; Noman, O.M.; Alqahtani, A.S.; Al-Zharani, M.; Alotaibi, A.A.; Daradka, H.M.; Al-Mishari, A.A.; Alobaid, W.A.; Alqahtani, A.; et al. Induction of apoptosis and cell cycle arrest by chloroform fraction of Juniperus phoenicea and chemical constituents analysis. Open Chem. 2021, 19, 119–127.
  156. Machana, S.; Weerapreeyakul, N.; Barusrux, S.; Nonpunya, A.; Sripanidkulchai, B.; Thitimetharoch, T. Cytotoxic and apoptotic effects of six herbal plants against the human hepatocarcinoma (HepG2) cell line. Chin. Med. 2011, 6, 2–9.
  157. MacHana, S.; Weerapreeyakul, N.; Barusrux, S.; Thumanu, K.; Tanthanuch, W. FTIR microspectroscopy discriminates anticancer action on human leukemic cells by extracts of Pinus kesiya; Cratoxylum formosum ssp. pruniflorum and melphalan. Talanta 2012, 93, 371–382.
  158. Thu, N.B.; Trung, T.N.; Ha, D.T.; Khoi, N.M.; Hung, T.V.; Hien, T.T.; Namhui, Y.; Bae, K. Screening of Vietnamese medicinal plants for cytotoxic activity. Nat. Prod. Sci. 2010, 16, 43–49.
  159. Chattopadhyay, S.K.; Kumar, T.R.S.; Maulik, P.R.; Srivastava, S.; Garg, A.; Sharon, A.; Negi, A.S.; Khanuja, S.P.S. Absolute configuration and anticancer activity of taxiresinol and related lignans of Taxus wallichiana. Bioorg. Med. Chem. 2003, 11, 4945–4948.
  160. Kaushik, P.; Lal Khokra, S.; Rana, A.C.; Kaushik, D. Evaluation of anticancer activity of Pinus roxburghii sarg. Against IMR-32 human neuroblastoma cancer cell line. Int. J. Pharm. Clin. Res. 2015, 7, 105–108.
  161. Jiang, P.; Zhang, Q.; Zhao, Y.; Xiong, J.; Wang, F.; Zhang, T.; Zhang, C. Extraction, Purification, and Biological Activities of Polysaccharides from Branches and Leaves of Taxus cuspidata S. Et Z. Molecules 2019, 24, 2926.
  162. Mukherjee, A.; Sikdar, S.; Bishayee, K.; Paul, A.; Ghosh, S.; Boujedaini, N.; Khuda-Bukhsh, A.R. Ethanolic extract of Thuja occidentalis blocks proliferation of A549 cells and induces apoptosis in vitro. J. Chin. Integr. Med. 2012, 10, 1451–1459.
  163. Khuda-Bukhsh, A.R.; Biswas, R.; Mandal, S.K.; Dutta, S.; Bhattacharyya, S.S.; Boujedaini, N. Thujone-rich fraction of Thuja occidentalis demonstrates major anti-cancer potentials: Evidences from in vitro studies on A375 cells. Evid. Based Complement. Altern. Med. 2011, 2011, 568148.
  164. Velmurugan, B.K.; Rathinasamy, B.; Lohanathan, B.P.; Thiyagarajan, V.; Weng, C.F. Neuroprotective role of phytochemicals. Molecules 2018, 23, 2485.
  165. Gitler, A.D.; Dhillon, P.; Shorter, J. Neurodegenerative disease: Models, mechanisms, and a new hope. DMM Dis. Model. Mech. 2017, 10, 499–502.
  166. Venkatesan, R.; Ji, E.; Kim, S.Y. Phytochemicals that regulate neurodegenerative disease by targeting neurotrophins: A comprehensive review. Biomed Res. Int. 2015, 2015, 814068.
  167. Johri, A.; Beal, M.F. Mitochondrial dysfunction in neurodegenerative diseases. J. Pharmacol. Exp. Ther. 2012, 342, 619–630.
  168. Yang, J.L.; Lin, Y.T.; Chuang, P.C.; Bohr, V.A.; Mattson, M.P. BDNF and exercise enhance neuronal DNA repair by stimulating CREB-mediated production of apurinic/apyrimidinic endonuclease 1. NeuroMol. Med. 2014, 16, 161–174.
  169. Huang, E.J.; Reichardt, L.F. Neurotrophins: Roles in neuronal development and function. Annu. Rev. Neurosci. 2001, 24, 677–736.
  170. Agrawal, M.; Biswas, A.; Levy, C.E. Molecular diagnostics of neurodegenerative disorders. Front. Mol. Biosci. 2015, 2, 1–10.
  171. Olivares, D.; Deshpande, V.K.; Shi, Y.; Lahiri, D.K.; Greig, N.H.; Rogers, J.T.; Huang, X. N-Methyl D-Aspartate (NMDA) Receptor Antagonists and Memantine Treatment for Alzheimer’s Disease, Vascular Dementia and Parkinson’s Disease. Curr. Alzheimer Res. 2012, 9, 746–758.
  172. Briffa, M.; Ghio, S.; Neuner, J.; Gauci, A.J.; Cacciottolo, R.; Marchal, C.; Caruana, M.; Cullin, C.; Vassallo, N.; Cauchi, R.J. Extracts from two ubiquitous Mediterranean plants ameliorate cellular and animal models of neurodegenerative proteinopathies. Neurosci. Lett. 2017, 638, 12–20.
  173. Physiology, G.; Waczulikova, I.; Kilanczyk, E.; Bryszewska, M. The effect of Pycnogenol on the erythrocyte membrane fluidity. Gen. Physiol. Biophys. 2004, 23, 39–51.
  174. Voss, P.; Horakova, L.; Jakstadt, M.; Kiekebusch, D.; Grune, T. Ferritin oxidation and proteasomal degradation: Protection by antioxidants. Free Radic. Res. 2006, 40, 673–683.
  175. Kim, C.S.; Subedi, L.; Kim, S.Y.; Choi, S.U.; Kim, K.H.; Lee, K.R. Diterpenes from the Trunk of Abies holophylla and Their Potential Neuroprotective and Anti-inflammatory Activities. J. Nat. Prod. 2016, 79, 387–394.
  176. Machado, F.D.; Kuo, J.; Ongaratti, B.R.; Medeiros, N.D.; Salvador, M.; Dani, C.; Funchal, C. Antioxidant and neuroprotective potential of extract of Brazilian pine Araucaria angustifolia bracts against oxidative stress induced by sodium azide in hippocampus. Integr. Pharmacol. Toxicol. Genotoxicol. 2015, 1, 16–20.
  177. Thiago, C.; Patrícia de Brum, V.; Patrícia Gomes da, S.; Marines de Avila, H.; Graziele Daiane, S.; Michele Stach, C.; Antônio Batista, P.; Sidnei, M.; Andreas Sebastian, M.; Chariston André Dal, B. Mechanism of the Entomotoxic Activity Induced by Araucaria Angustifolia Methanolic Extract in Nauphoeta Cinerea Lobster Cockroaches. J. Bot. Res. 2017, 1, 38–49.
  178. Zhao, Z.; Dong, Z.; Ming, J.; Liu, Y. Cedrin identified from Cedrus deodara (Roxb.) G. Don protects PC12 cells against neurotoxicity. Nat. Prod. Res. 2018, 6419, 1455–1458.
  179. Lee, J.S.; Kim, H.G.; Lee, H.W.; Han, J.M.; Lee, S.K.; Kim, D.W.; Saravanakumar, A.; Son, C.G. Hippocampal memory enhancing activity of pine needle extract against scopolamine-induced amnesia in a mouse model. Sci. Rep. 2015, 5, 1–10.
  180. Lee, J.S.; Kim, H.G.; Lee, H.W.; Kim, W.Y.; Ahn, Y.C.; Son, C.G. Pine needle extract prevents hippocampal memory impairment in acute restraint stress mouse model. J. Ethnopharmacol. 2017, 207, 226–236.
  181. Forouzanfar, F.; Ghorbani, A.; Hosseini, M. Hydroalcoholic extract of needles of Pinus eldarica enhances pentobarbital-induced sleep: Possible involvement of GABAergic system. Avicenna J. Phytomed. 2016, 6, 449.
  182. Wang, C.; He, L.; Yan, M. Effects of polyprenols from pine needles of Pinus massoniana on ameliorating cognitive impairment in a D -galactose-induced mouse model. Age 2014, 36, 9676.
  183. Khan, M.M.; Kempuraj, D.; Thangavel, R.; Zaheer, A. Protection of MPTP-induced neuroinflammation and neurodegeneration by Pycnogenol. Neurochem. Int. 2013, 62, 379–388.
  184. Kabra, A.; Baghel, U.S.; Hano, C.; Martins, N.; Khalid, M.; Sharma, R. Neuroprotective potential of Myrica esulenta in Haloperidol induced Parkinson’s disease. J. Ayurveda Integr. Med. 2020, 11, 448–454.
  185. Lokesh, D.; Amitabha, D.; Sachin, A.; Avijeet, J. Neuropharmacological Exploration of Thuja Occidentalis Linn. Int. Res. J. Pharm. 2011, 2, 143–148.
  186. Lee, S.; Choi, C.; Kim, J.; Lim, S.; Jung, H. The Antioxidant Activities and Neuroprotective Effects of Hot Water Extracts from Torreyae Semen. Korea J. Herbol. 2017, 32, 41–48.
  187. Deture, M.A.; Dickson, D.W. The neuropathological diagnosis of Alzheimer’s disease. Mol. Neurodegener. 2019, 14, 1–18.
  188. Jahn, H. Memory loss in Alzheimer’s disease. Dialogues Clin. Neurosci. 2013, 15, 445–454.
  189. Tanvir Kabir, M.; Sahab Uddin, M.; Al Mamun, A.; Jeandet, P.; Aleya, L.; Mansouri, R.A.; Md Ashraf, G.; Mathew, B.; Bin-Jumah, M.N.; Abdel-Daim, M.M. Combination drug therapy for the management of alzheimer’s disease. Int. J. Mol. Sci. 2020, 21, 3272.
  190. Durães, F.; Pinto, M.; Sousa, E. Old drugs as new treatments for neurodegenerative diseases. Pharmaceuticals 2018, 11, 44.
  191. Barbier, P.; Zejneli, O.; Martinho, M.; Lasorsa, A.; Belle, V.; Smet-Nocca, C.; Tsvetkov, P.O.; Devred, F.; Landrieu, I. Role of tau as a microtubule-associated protein: Structural and functional aspects. Front. Aging Neurosci. 2019, 10, 1–14.
  192. Cory, H.; Passarelli, S.; Szeto, J.; Tamez, M.; Mattei, J. The Role of Polyphenols in Human Health and Food Systems: A Mini-Review. Front. Nutr. 2018, 5, 1–9.
  193. Rensink, A.A.M.; De Waal, R.M.W.; Kremer, B.; Verbeek, M.M. Pathogenesis of cerebral amyloid angiopathy. Brain Res. Rev. 2003, 43, 207–223.
  194. Tanaka, M.; Saito, S.; Inoue, T.; Satoh-Asahara, N.; Ihara, M. Novel therapeutic potentials of taxifolin for amyloid-β-associated neurodegenerative diseases and other diseases: Recent advances and future perspectives. Int. J. Mol. Sci. 2019, 20, 2139.
  195. Sharma, L.; Sharma, A.; Goyal, R.; Alam, J. Pinus roxburghii Sarg. Ameliorates alzheimer’s disease-type neurodegeneration and cognitive deficits caused by intracerebroventricular-streptozotocin in rats: An in vitro and in vivo study. Indian J. Pharm. Sci. 2020, 82, 861–870.
  196. Hassaan, Y.; Handoussa, H.; El-Khatib, A.H.; Linscheid, M.W.; El Sayed, N.; Ayoub, N. Evaluation of plant phenolic metabolites as a source of Alzheimer’s drug leads. Biomed Res. Int. 2014, 2014, 843263.
  197. Arbo, B.D.; André-Miral, C.; Nasre-Nasser, R.G.; Schimith, L.E.; Santos, M.G.; Costa-Silva, D.; Muccillo-Baisch, A.L.; Hort, M.A. Resveratrol Derivatives as Potential Treatments for Alzheimer’s and Parkinson’s Disease. Front. Aging Neurosci. 2020, 12, 1–15.
  198. Ahmed, T.; Javed, S.; Javed, S.; Tariq, A.; Šamec, D.; Tejada, S.; Nabavi, S.F.; Braidy, N.; Nabavi, S.M. Resveratrol and Alzheimer’s Disease: Mechanistic Insights. Mol. Neurobiol. 2017, 54, 2622–2635.
  199. Maimoona, A.; Naeem, I.; Saddiqe, Z.; Jameel, K. A review on biological, nutraceutical and clinical aspects of French maritime pine bark extract. J. Ethnopharmacol. 2011, 133, 261–277.
  200. Peng, Q.L.; Zard, A.R.B.; Lau, B.H.S. Pycnogenol protects neurons from amyloid- b peptide-induced apoptosis. Mol. Brain Res. 2002, 104, 55–65.
  201. Paarmann, K.; Prakash, S.R.; Krohn, M.; Möhle, L.; Brackhan, M.; Brüning, T.; Eiriz, I.; Pahnke, J. French maritime pine bark treatment decelerates plaque development and improves spatial memory in Alzheimer’s disease mice. Phytomedicine 2019, 57, 39–48.
  202. Fang, C.; Lv, L.; Mao, S.; Dong, H.; Liu, B. Cognition Deficits in Parkinson’s Disease: Mechanisms and Treatment. Parkinsons Dis. 2020, 2020, 2076942.
  203. Dias, V.; Junn, E.; Mouradian, M.M. The role of oxidative stress in parkinson’s disease. J. Parkinsons Dis. 2013, 3, 461–491.
  204. Chen, L.; Ding, Y.; Cagniard, B.; Van Laar, A.D.; Mortimer, A.; Chi, W.; Hastings, T.G.; Un, J.K.; Zhuang, X. Unregulated cytosolic dopamine causes neurodegeneration associated with oxidative stress in mice. J. Neurosci. 2008, 28, 425–433.
  205. Zoccarato, F.; Toscano, P.; Alexandre, A. Dopamine-derived dopaminochrome promotes H2O2 release at mitochondrial Complex I: Stimulation by rotenone, control by Ca2+, and relevance to Parkinson disease. J. Biol. Chem. 2005, 280, 15587–15594.
  206. Ebrahimi-Fakhari, D.; Wahlster, L.; McLean, P.J. Protein degradation pathways in Parkinson’s disease: Curse or blessing. Acta Neuropathol. 2012, 124, 153–172.
  207. Javed, H.; Nagoor Meeran, M.F.; Azimullah, S.; Adem, A.; Sadek, B.; Ojha, S.K. Plant Extracts and Phytochemicals Targeting α-Synuclein Aggregation in Parkinson’s Disease Models. Front. Pharmacol. 2019, 9, 1555.
  208. Corona, J.C. Natural Compounds for the Management of Parkinson’s Disease and Attention-Deficit/Hyperactivity Disorder. Biomed Res. Int. 2018, 2018, 4067597.
  209. Ríos, J.L.; Onteniente, M.; Picazo, D.; Montesinos, M.C. Medicinal Plants and Natural Products as Potential Sources for Antiparkinson Drugs. Planta Med. 2016, 82, 942–951.
  210. Bais, S.; Gill, N.S.; Kumar, N. Neuroprotective Effect of Juniperus communis on Chlorpromazine Induced Parkinson Disease in Animal Model. Chin. J. Biol. 2015, 2015, 1–7.
  211. Zhang, F.; Shi, J.S.; Zhou, H.; Wilson, B.; Hong, J.S.; Gao, H.M. Resveratrol protects dopamine neurons against lipopolysaccharide-induced neurotoxicity through its anti-inflammatory actions. Mol. Pharmacol. 2010, 78, 466–477, reprinted in Mol. Pharmacol. 2010, 78, 981.
  212. Fang, X.S.; Hao, J.F.; Zhou, H.Y.; Zhu, L.X.; Wang, J.H.; Song, F.Q. Pharmacological studies on the sedative-hypnotic effect of Semen Ziziphi spinosae (Suanzaoren) and Radix et Rhizoma Salviae miltiorrhizae (Danshen) extracts and the synergistic effect of their combinations. Phytomedicine 2010, 17, 75–80.
  213. Akram, M.; Daniyal, M.; Munir, N.; Mohiuddin, E.; Sultana, S. Medicinal Plants Combating Against Insomnia: A Green Anti-Insomnia Approach. J. Nerv. Ment. Dis. 2019, 207, 927–935.
  214. Gooneratne, N.S.; Vitiello, M.V. Sleep in Older Adults. Normative Changes, Sleep Disorders, and Treatment Options. Clin. Geriatr. Med. 2014, 30, 591–627.
  215. Atkin, T.; Comai, S.; Gobbi, G. Drugs for insomnia beyond benzodiazepines: Pharmacology, clinical applications, and discovery. Pharmacol. Rev. 2018, 70, 197–245.
  216. Sateia, M.J.; Buysse, D.J.; Krystal, A.D.; Neubauer, D.N. Adverse effects of hypnotic medications. J. Clin. Sleep Med. 2017, 13, 839.
  217. Woo, J.; Yang, H.; Yoon, M.; Gadhe, C.G.; Pae, A.N.; Cho, S.; Justin Lee, C. 3-Carene, a phytoncide from pine tree has a sleep-enhancing effect by targeting the GABAA-benzodiazepine receptors. Exp. Neurobiol. 2019, 28, 593–601.
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